Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA‐, α₁‐ and 5‐HT2A‐receptors

The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 – 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 – 3 mg kg −1 s.c.) caused a marked dose‐dependent increase in EEG power in the frontal cortex at 1 – 3 Hz with decreases in power at higher frequencies (9 – 30 Hz). At high doses (3 mg kg −1 s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 – 0.1 mg kg −1 i.p.) caused similar effects but with lesser changes in power. In contrast, the non‐competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 – 10 mg kg −1 i.p.) The atypical antipsychotic clozapine (0.2 mg kg −1 s.c.) synchronized the EEG (peak 8 Hz). The 5‐HT 2A ‐antagonist, M100907, specifically increased EEG power at 2 – 3 Hz at low doses (10 and 50 μg kg ÷1 s.c.), whereas at higher doses (0.1 mg kg −1 s.c.) the profile resembled that of clozapine. Clozapine (0.2 mg kg −1 s.c.), GYKI 53655 (5 mg kg −1 i.p.), prazosin (0.05 and 0.1 mg kg −1 i.p.), and M100907 (0.01 and 0.05 mg kg −1 s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg −1 s.c.), but not the increase in power at 1 – 3 Hz in prefrontal cortex. British Journal of Pharmacology (2002) 135 , 65–78; doi: 10.1038/sj.bjp.0704451